Influenza A, Influenza B
Conditions
Keywords
Antiviral, IVIG, Hemagglutination inhibition (HAI), Antibody
Brief summary
Influenza (the flu) is a common illness that usually occurs in autumn and winter. The flu is usually mild, but can cause serious illness or death. The purpose of this study is to test the safety and effectiveness of an antibody against the flu (called intravenous hyperimmune immunoglobulin or IVIG) in people who are hospitalized for severe flu.
Detailed description
Influenza is responsible for thousands of hospitalizations and deaths each year in the United States and worldwide. One possible new treatment for the flu involves the use of IVIG, a blood product containing antibodies from people who have recovered from the flu or who have had a flu shot. The purpose of this study is to evaluate whether IVIG can reduce the severity and duration of flu in people who are hospitalized with the flu. The study will enroll participants 18 years and older who are hospitalized with the flu. The study will enroll participants over one or more flu seasons. Regardless of the date of enrollment, each participant will be in the study for about 28 days. At study entry (Day 0), participants will be randomly assigned to one of two groups (Arms A and B). Participants in both groups will receive standard of care (SOC) treatment for the flu, but those in Arm A will also receive one dose of IVIG and those in Arm B will receive a placebo for IVIG. Both IVIG and placebo will be given intravenously over at least 2 hours. On Day 0, before receiving IVIG or placebo, participants will undergo a symptoms assessment, blood collection, and a nasopharyngeal (NP) swab to collect a sample of secretions from the nose and throat. Additional study visits will occur on Days 1, 2, 3, 7, 14, and 28. Depending on the visit, participants may take part in the same study procedures that took place on Day 0. On Days 2, 14, and 28, visits for participants who are no longer hospitalized may be conducted over the phone.
Interventions
BIOLOGICALIntravenous hyperimmune immunoglobulin (IVIG)
Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight)
BIOLOGICALPlacebo for IVIG
Administered IV as 500 mL of normal saline
Sponsors
University of Minnesota
International Network for Strategic Initiatives in Global HIV Trials (INSIGHT)
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent * Locally determined positive influenza test (by polymerase chain reaction \[PCR\] or other nucleic acid test, or by rapid antigen \[Ag\]) from a specimen obtained within 2 days prior to randomization * Onset of illness no more than 7 days before randomization, defined as when the participant first experienced at least one respiratory symptom or fever * Hospitalized (or in observation unit) for influenza, with anticipated hospitalization for more than 24 hours. Criteria for hospitalization will be up to the individual treating clinician. * For women of child-bearing potential: willingness to abstain from sexual intercourse or use at least one form of hormonal or barrier contraception through Day 28 of the study * Willingness to have blood and respiratory samples obtained and stored * NEW score greater than or equal to 2 at screening (see the protocol for more information on this criterion)
Exclusion criteria
* Women who are pregnant or breast-feeding * Strong clinical evidence (in the judgment of the site investigator) that the etiology of illness is primarily bacterial in origin * Prior treatment with any investigational drug therapy within 30 days prior to screening * History of allergic reaction to blood or plasma products (as judged by the site investigator) * Known immunoglobulin A (IgA) deficiency * A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the participant at a substantially increased risk of thrombosis (e.g., cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy) * Presence of any pre-existing illness that, in the opinion of the site investigator, would place the participant at an unreasonably increased risk through participation in this study * Participants who, in the judgment of the site investigator, will be unlikely to comply with the requirements of this protocol * Medical conditions for which receipt of a 500 mL volume of intravenous fluid may be dangerous to the participant (e.g., decompensated congestive heart failure) * Receiving extracorporeal membrane oxygenation (ECMO) * Suspicion that infection is due to an influenza strain or subtype other than A(H1N1)pdm09, H3N2, or influenza B (e.g., H5N1, H7N9)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients in Each of 6 Clinical Status Categories on Day 7 | Assessed on Day 7 | This is the primary outcome, a 6-category ordinal outcome ranging from death (worst) to discharged from hospital with resumption of normal activities (best). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients in Each of 6 Clinical Status Categories on Day 3 | Measured on Day 3 | 6-category ordinal outcome evaluated on Day 3; clinical status ranges from death (worst) to discharged from hospital with resumption of normal activities (best). |
| Number of Patients With a Favorable Outcome on Day 7 | Assessed on Day 7 | Sliding dichotomy defined as non-ICU hospitalization or discharge if enrolled from ICU, and discharge if enrolled from the general ward. |
| Hospital Discharge | Measured through Day 7 | Number of participants alive and discharged from the hospital |
| Mortality | Measured through day 28 | Number of participants dying through day 28. |
| Number of Patients Alive and Out of Hospital | Measured through Day 28 | Number and percent alive and out of hospital on day 28 |
| Change in Viral Load | Day 3 | Change in nasopharyngeal viral load from baseline to day 3 |
| Death or Re-hospitalization | Day 28 | Number and percent of participants who died or were re-hospitalized after initial discharge |
| Percent of Participants Developing Complications | Measured through Day 28 | Number and percent of participants developing respiratory distress syndrome, acute renal failure, sepsis, pneumonia, enteritis, or bronchitis |
| Number of Patients in Each of 5 Clinical Status Categories on Day 3 | Assessed on Day 3 | 5-category ordinal outcome assessed on day 3; clinical status ranges from death (worst) to discharged from the hospital (best). |
| Number of Patients Alive and Out of Hospital on Day 14 | day 14 | Number and percentage of participants alive and out of the hospital on Day 14 |
| Resumption of Normal Activities by Day 14 | day 14 | Participants reporting resumption of normal daily activities by Day 14 |
| Number of Patients in Each of 6 Clinical Status Categories on Day 28 | day 28 | 6-category ordinal outcome corresponding to clinical status on day 28 |
| Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Day 7 | Primary 6-category ordinal outcome for participants infected with Influenza A |
| Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Day 7 | Primary 6-category ordinal outcome for subgroup of participants infected with influenza B |
| pH1N1 Titers at Day 7 | Day 7 | pH1N1 hemagglutination inhibition assay (HAI) titers among participants infected with pH1N1 using A/Cal/2009 as reference virus |
| H3N2 Titers at Day 7 | Day 7 | H3N2 HAI titers among participants infected with H3N2 using A/HongKong/2014 as reference virus |
| Influenza B Titers at Day 7 | Day 7 | Flu B HAI titers among participants infected with influenza B using B/Phuket/2013 as reference virus |
| Number of Patients in Each of 6 Clinical Status Categories on Day 14 | Measured on day 14 | 6-category ordinal outcome measured on day 14 |
Countries
Australia, Denmark, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A: hIVIG Participants will receive a single infusion of intravenous hyperimmune immunoglobulin (hIVIG), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu.
Intravenous hyperimmune immunoglobulin (IVIG): Administered intravenously (IV) at a dose of 0.25 g/kg (up to a maximum of 24.75 g, corresponding to approximately 100 kg actual body weight) | 156 |
| Arm B: Placebo Participants will receive a single infusion of placebo for IVIG (saline), administered over approximately 2 hours on Day 0. Participants will also receive SOC treatment for the flu.
Placebo for IVIG: Administered IV as 500 mL of normal saline | 152 |
| Total | 308 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 12 | 9 |
Baseline characteristics
| Characteristic | Arm A: hIVIG | Arm B: Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical >=65 years | 46 Participants | 51 Participants | 97 Participants |
| Age, Categorical Between 18 and 65 years | 109 Participants | 100 Participants | 209 Participants |
| Age, Continuous | 55 years | 57 years | 57 years |
| National Early Warning (NEW) score | 4 units on a scale | 4 units on a scale | 4 units on a scale |
| Race/Ethnicity, Customized Race/ethnicity Asian | 33 Participants | 36 Participants | 69 Participants |
| Race/Ethnicity, Customized Race/ethnicity Black/African American | 27 Participants | 30 Participants | 57 Participants |
| Race/Ethnicity, Customized Race/ethnicity Hispanic | 27 Participants | 24 Participants | 51 Participants |
| Race/Ethnicity, Customized Race/ethnicity Other | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race/ethnicity White/Caucasian | 67 Participants | 61 Participants | 128 Participants |
| Region of Enrollment Argentina | 4 Participants | 4 Participants | 8 Participants |
| Region of Enrollment Australia | 5 Participants | 5 Participants | 10 Participants |
| Region of Enrollment Denmark | 5 Participants | 3 Participants | 8 Participants |
| Region of Enrollment Greece | 5 Participants | 4 Participants | 9 Participants |
| Region of Enrollment Mexico | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment Spain | 5 Participants | 5 Participants | 10 Participants |
| Region of Enrollment Thailand | 32 Participants | 35 Participants | 67 Participants |
| Region of Enrollment United Kingdom | 8 Participants | 10 Participants | 18 Participants |
| Region of Enrollment United States | 91 Participants | 84 Participants | 175 Participants |
| Sex: Female, Male Female | 80 Participants | 88 Participants | 168 Participants |
| Sex: Female, Male Male | 76 Participants | 64 Participants | 140 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 156 | 5 / 152 |
| other Total, other adverse events | 13 / 156 | 14 / 152 |
| serious Total, serious adverse events | 25 / 156 | 26 / 152 |
Outcome results
Primary
Number of Patients in Each of 6 Clinical Status Categories on Day 7
This is the primary outcome, a 6-category ordinal outcome ranging from death (worst) to discharged from hospital with resumption of normal activities (best).
Time frame: Assessed on Day 7
Population: All infused participants, using multiple imputation to impute outcome for 4 participants with missing data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 7 | Died | 3 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 7 | Hospitalized, in ICU | 6 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 7 | Non-ICU hospitalization, using supplemental oxygen | 15 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 7 | Non-ICU hospitalization, no supplemental oxygen | 8 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 7 | Discharged, not back to normal activities | 56 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 7 | Discharged, back to normal activities | 68 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 7 | Discharged, not back to normal activities | 51 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 7 | Died | 2 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 7 | Non-ICU hospitalization, no supplemental oxygen | 12 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 7 | Hospitalized, in ICU | 11 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 7 | Discharged, back to normal activities | 60 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 7 | Non-ICU hospitalization, using supplemental oxygen | 16 Participants |
Comparison: Odds ratio of being in a better category, as assessed using a proportional odds model. Multiple imputation techniques were used to impute an outcome for 4 patients for whom the outcome was unknown.p-value: 0.3395% CI: [0.79, 1.97]Regression, Logistic
Secondary
Change in Viral Load
Change in nasopharyngeal viral load from baseline to day 3
Time frame: Day 3
Population: Participants with viral load results at both baseline and day 3. Participants with undetectable viral load results at baseline are excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: hIVIG | Change in Viral Load | -1.99 log10 RNA | Standard Error 0.16 |
| Arm B: Placebo | Change in Viral Load | -2.32 log10 RNA | Standard Error 0.17 |
p-value: 0.4995% CI: [-0.26, 0.54]Regression, Linear
Secondary
Death or Re-hospitalization
Number and percent of participants who died or were re-hospitalized after initial discharge
Time frame: Day 28
Population: all participants with data
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: hIVIG | Death or Re-hospitalization | 19 Participants |
| Arm B: Placebo | Death or Re-hospitalization | 19 Participants |
p-value: 0.9395% CI: [0.5, 1.97]Regression, Logistic
Secondary
H3N2 Titers at Day 7
H3N2 HAI titers among participants infected with H3N2 using A/HongKong/2014 as reference virus
Time frame: Day 7
Population: participants infected with H3N2 with HAI titers measured at day 7
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: hIVIG | H3N2 Titers at Day 7 | 259 titer | Standard Deviation 291 |
| Arm B: Placebo | H3N2 Titers at Day 7 | 225 titer | Standard Deviation 277 |
p-value: 0.1395% CI: [0.93, 1.8]Mixed Models Analysis
Secondary
Hospital Discharge
Number of participants alive and discharged from the hospital
Time frame: Measured through Day 7
Population: All participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: hIVIG | Hospital Discharge | Not discharged alive | 37 Participants |
| Arm A: hIVIG | Hospital Discharge | Discharged alive | 119 Participants |
| Arm B: Placebo | Hospital Discharge | Not discharged alive | 42 Participants |
| Arm B: Placebo | Hospital Discharge | Discharged alive | 110 Participants |
Comparison: Deaths during hospitalization are censored after day 7.p-value: 0.4495% CI: [0.85, 1.45]Regression, Cox
Secondary
Influenza B Titers at Day 7
Flu B HAI titers among participants infected with influenza B using B/Phuket/2013 as reference virus
Time frame: Day 7
Population: participants infected with influenza B with HAI titers measured at day 7
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: hIVIG | Influenza B Titers at Day 7 | 112 titer | Standard Deviation 161 |
| Arm B: Placebo | Influenza B Titers at Day 7 | 84 titer | Standard Deviation 83 |
p-value: 0.7895% CI: [0.58, 1.5]Mixed Models Analysis
Secondary
Mortality
Number of participants dying through day 28.
Time frame: Measured through day 28
Population: all participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: hIVIG | Mortality | Died | 6 Participants |
| Arm A: hIVIG | Mortality | Did not die | 150 Participants |
| Arm B: Placebo | Mortality | Died | 5 Participants |
| Arm B: Placebo | Mortality | Did not die | 147 Participants |
p-value: 0.495% CI: [0.48, 6.15]Regression, Cox
Secondary
Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7
Primary 6-category ordinal outcome for participants infected with Influenza A
Time frame: Day 7
Population: all participants infected with influenza A
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: hIVIG | Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Died | 3 Participants |
| Arm A: hIVIG | Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Hospitalized in ICU | 5 Participants |
| Arm A: hIVIG | Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Hospitalized on supplemental oxygen | 14 Participants |
| Arm A: hIVIG | Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Hospitalized not on supplemental oxygen | 7 Participants |
| Arm A: hIVIG | Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Discharged, not back to normal activities | 40 Participants |
| Arm A: hIVIG | Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Discharged, back to normal activities | 45 Participants |
| Arm B: Placebo | Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Discharged, not back to normal activities | 39 Participants |
| Arm B: Placebo | Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Died | 0 Participants |
| Arm B: Placebo | Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Hospitalized not on supplemental oxygen | 10 Participants |
| Arm B: Placebo | Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Hospitalized in ICU | 7 Participants |
| Arm B: Placebo | Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Discharged, back to normal activities | 45 Participants |
| Arm B: Placebo | Number of Influenza A-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Hospitalized on supplemental oxygen | 9 Participants |
Comparison: Multiple imputation was used to estimate the outcome for 3 participants for whom the outcome was partially unknown.p-value: 0.8295% CI: [0.55, 1.59]Regression, Logistic
Secondary
Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7
Primary 6-category ordinal outcome for subgroup of participants infected with influenza B
Time frame: Day 7
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: hIVIG | Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Died | 0 Participants |
| Arm A: hIVIG | Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Hospitalized in ICU | 1 Participants |
| Arm A: hIVIG | Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Hospitalized on supplemental oxygen | 1 Participants |
| Arm A: hIVIG | Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Hospitalized not on supplemental oxygen | 1 Participants |
| Arm A: hIVIG | Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Discharged, not back to normal activities | 16 Participants |
| Arm A: hIVIG | Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Discharged, back to normal activities | 23 Participants |
| Arm B: Placebo | Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Discharged, not back to normal activities | 12 Participants |
| Arm B: Placebo | Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Died | 2 Participants |
| Arm B: Placebo | Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Hospitalized not on supplemental oxygen | 2 Participants |
| Arm B: Placebo | Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Hospitalized in ICU | 4 Participants |
| Arm B: Placebo | Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Discharged, back to normal activities | 15 Participants |
| Arm B: Placebo | Number of Influenza B-Infected Patients in Each of 6 Clinical Status Categories on Day 7 | Hospitalized on supplemental oxygen | 7 Participants |
Comparison: Multiple imputation was used to estimate the outcome for one participant.p-value: 0.0295% CI: [1.21, 8.42]Regression, Logistic
Secondary
Number of Patients Alive and Out of Hospital
Number and percent alive and out of hospital on day 28
Time frame: Measured through Day 28
Population: All participants with vital status known on Day 28
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: hIVIG | Number of Patients Alive and Out of Hospital | Alive and out of hospital | 140 Participants |
| Arm A: hIVIG | Number of Patients Alive and Out of Hospital | Died or hospitalized | 15 Participants |
| Arm B: Placebo | Number of Patients Alive and Out of Hospital | Alive and out of hospital | 137 Participants |
| Arm B: Placebo | Number of Patients Alive and Out of Hospital | Died or hospitalized | 14 Participants |
p-value: 0.7495% CI: [0.38, 1.98]Regression, Logistic
Secondary
Number of Patients Alive and Out of Hospital on Day 14
Number and percentage of participants alive and out of the hospital on Day 14
Time frame: day 14
Population: all participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: hIVIG | Number of Patients Alive and Out of Hospital on Day 14 | 134 Participants |
| Arm B: Placebo | Number of Patients Alive and Out of Hospital on Day 14 | 125 Participants |
p-value: 0.7795% CI: [0.5, 2.31]Regression, Logistic
Secondary
Number of Patients in Each of 5 Clinical Status Categories on Day 3
5-category ordinal outcome assessed on day 3; clinical status ranges from death (worst) to discharged from the hospital (best).
Time frame: Assessed on Day 3
Population: All participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: hIVIG | Number of Patients in Each of 5 Clinical Status Categories on Day 3 | Hospitalized, in ICU | 8 Participants |
| Arm A: hIVIG | Number of Patients in Each of 5 Clinical Status Categories on Day 3 | Non-ICU hospitalization, NEW score < 3 | 55 Participants |
| Arm A: hIVIG | Number of Patients in Each of 5 Clinical Status Categories on Day 3 | Non-ICU hospitalization, NEW score 3+ | 25 Participants |
| Arm A: hIVIG | Number of Patients in Each of 5 Clinical Status Categories on Day 3 | Discharged | 67 Participants |
| Arm A: hIVIG | Number of Patients in Each of 5 Clinical Status Categories on Day 3 | Death | 1 Participants |
| Arm B: Placebo | Number of Patients in Each of 5 Clinical Status Categories on Day 3 | Discharged | 62 Participants |
| Arm B: Placebo | Number of Patients in Each of 5 Clinical Status Categories on Day 3 | Death | 0 Participants |
| Arm B: Placebo | Number of Patients in Each of 5 Clinical Status Categories on Day 3 | Hospitalized, in ICU | 13 Participants |
| Arm B: Placebo | Number of Patients in Each of 5 Clinical Status Categories on Day 3 | Non-ICU hospitalization, NEW score 3+ | 31 Participants |
| Arm B: Placebo | Number of Patients in Each of 5 Clinical Status Categories on Day 3 | Non-ICU hospitalization, NEW score < 3 | 46 Participants |
Comparison: Odds ratio for being in a better category, from a proportional odds modelp-value: 0.8495% CI: [0.61, 1.48]Regression, Logistic
Secondary
Number of Patients in Each of 6 Clinical Status Categories on Day 14
6-category ordinal outcome measured on day 14
Time frame: Measured on day 14
Population: participants with observed data on day 14
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 14 | Died | 4 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 14 | Hospitalized in ICU | 5 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 14 | Hospitalized on supplement oxygen | 8 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 14 | Hospitalized not on supplemental oxygen | 4 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 14 | Discharged, not back to normal activities | 29 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 14 | Discharged, back to normal activities | 102 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 14 | Discharged, not back to normal activities | 33 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 14 | Died | 4 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 14 | Hospitalized not on supplemental oxygen | 11 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 14 | Hospitalized in ICU | 6 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 14 | Discharged, back to normal activities | 92 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 14 | Hospitalized on supplement oxygen | 5 Participants |
Comparison: Proportional odds for being in a better categoryp-value: 0.5595% CI: [0.7, 1.95]Regression, Logistic
Secondary
Number of Patients in Each of 6 Clinical Status Categories on Day 28
6-category ordinal outcome corresponding to clinical status on day 28
Time frame: day 28
Population: participants with observed data
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 28 | Died | 6 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 28 | Hospitalized in ICU | 2 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 28 | Hospitalized, on supplemental oxygen | 6 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 28 | Hospitalized, not on supplemental oxygen | 1 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 28 | Discharged, not back to normal activities | 21 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 28 | Discharged, back to normal activities | 115 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 28 | Discharged, not back to normal activities | 22 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 28 | Died | 5 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 28 | Hospitalized, not on supplemental oxygen | 5 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 28 | Hospitalized in ICU | 2 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 28 | Discharged, back to normal activities | 114 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 28 | Hospitalized, on supplemental oxygen | 2 Participants |
p-value: 0.7395% CI: [0.5, 1.62]Regression, Logistic
Secondary
Number of Patients in Each of 6 Clinical Status Categories on Day 3
6-category ordinal outcome evaluated on Day 3; clinical status ranges from death (worst) to discharged from hospital with resumption of normal activities (best).
Time frame: Measured on Day 3
Population: All participants with clinical data available on Day 3
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 3 | Death | 1 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 3 | Hospitalized, in ICU | 8 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 3 | Non-ICU hospitalization, on supplemental oxygen | 37 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 3 | Non-ICU hospitalizaiton, no supplemental oxygen | 43 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 3 | Discharged, not back to normal activities | 53 Participants |
| Arm A: hIVIG | Number of Patients in Each of 6 Clinical Status Categories on Day 3 | Discharged, back to normal activities | 13 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 3 | Discharged, not back to normal activities | 53 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 3 | Death | 0 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 3 | Non-ICU hospitalizaiton, no supplemental oxygen | 43 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 3 | Hospitalized, in ICU | 13 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 3 | Discharged, back to normal activities | 9 Participants |
| Arm B: Placebo | Number of Patients in Each of 6 Clinical Status Categories on Day 3 | Non-ICU hospitalization, on supplemental oxygen | 34 Participants |
Comparison: Odds ratio for being in a better group, from a proportional odds model.p-value: 0.5295% CI: [0.57, 1.33]Regression, Cox
Secondary
Number of Patients With a Favorable Outcome on Day 7
Sliding dichotomy defined as non-ICU hospitalization or discharge if enrolled from ICU, and discharge if enrolled from the general ward.
Time frame: Assessed on Day 7
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: hIVIG | Number of Patients With a Favorable Outcome on Day 7 | favorable outcome | 128 Participants |
| Arm A: hIVIG | Number of Patients With a Favorable Outcome on Day 7 | unfavorable outcome | 28 Participants |
| Arm B: Placebo | Number of Patients With a Favorable Outcome on Day 7 | unfavorable outcome | 37 Participants |
| Arm B: Placebo | Number of Patients With a Favorable Outcome on Day 7 | favorable outcome | 115 Participants |
p-value: 0.295% CI: [0.81, 2.74]Regression, Logistic
Secondary
Percent of Participants Developing Complications
Number and percent of participants developing respiratory distress syndrome, acute renal failure, sepsis, pneumonia, enteritis, or bronchitis
Time frame: Measured through Day 28
Population: all participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: hIVIG | Percent of Participants Developing Complications | 20 Participants |
| Arm B: Placebo | Percent of Participants Developing Complications | 22 Participants |
p-value: 0.8195% CI: [0.5, 1.82]Regression, Logistic
Secondary
pH1N1 Titers at Day 7
pH1N1 hemagglutination inhibition assay (HAI) titers among participants infected with pH1N1 using A/Cal/2009 as reference virus
Time frame: Day 7
Population: participants infected with pH1N1 with HAI titers measured at day 7
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: hIVIG | pH1N1 Titers at Day 7 | 285 titer | Standard Deviation 374 |
| Arm B: Placebo | pH1N1 Titers at Day 7 | 229 titer | Standard Deviation 341 |
Comparison: HAI measurements were log-transformed to compute treatment differences and the model was adjusted for baseline titer.p-value: 0.1895% CI: [0.84, 2.7]Mixed Models Analysis
Secondary
Resumption of Normal Activities by Day 14
Participants reporting resumption of normal daily activities by Day 14
Time frame: day 14
Population: Participants with observed data
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: hIVIG | Resumption of Normal Activities by Day 14 | 102 Participants |
| Arm B: Placebo | Resumption of Normal Activities by Day 14 | 92 Participants |
p-value: 0.3495% CI: [0.7, 2.34]Regression, Logistic